I. Ability of peptides to function as bombesin receptor antagonists at the difference receptor subtypes. Two different receptors the gastrin-releasing peptide receptor (GRP-R) and neuromedin B receptor (NMB-R) mediate the action of bombesin- related peptides in mammals. We have developed 6 classes of GRP receptor antagonists but have only identified one class of NMB-R antagonists of low affinity. To attempt to find additional classes of NMB-R antagonists we have applied a number of the strategies applied to the GRP-receptor to NMB related peptides. The formation of COOH terminal truncated NMB peptides of different classes (amides, esters, alkyl amides); various pseudopeptides, D-amino substituted peptides or NH2 terminal truncated NMB analogues all did not result in any potent NMR-R antagonists: These results demonstrate that despite the fact GRP and NMB related peptides differ in only 2 amino acids and the receptors have 50% homology, the structure-function relationships and active comfirmations of the two receptors are markedly different. Novel strategies will have to be developed to produce NMB receptor antagonists.